a study of at1001 (migalastat hydrochloride) in participants with fabry disease

Conditions: Fabry Disease

Summary: study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of migalastat hydrochloride (hcl) (migalastat) in participants with fabry disease.

this was a phase 2, open-label study in male participants with fabry disease. all participants who met initial eligibility criteria underwent a 28-day screening period, including a 14-day run-in with migalastat (150 milligrams \[mg\] migalastat once a day \[qd\] from days -28 to -15) to assess eligibility for entering the treatment period of the study. participants who entered the treatment period were required to have α-galactosidase a (α-gal a) activity responsive to migalastat. fifteen participants received at least 1 dose of study drug, however, 6 of these participants did not demonstrate α-gal a activity responsive to migalastat and were thus screen failures (these participants are hereafter referred to as "dosed screen failures") due to not meeting all inclusion criteria for treatment. therefore, 9 participants were enrolled into the treatment period (these participants are hereafter referred to as "eligible-enrolled"). eligible-enrolled participants (those who satisfied the criteria for inclusion in the study) received escalating doses of migalastat twice a day (bid) for 6 weeks (days 1 to 42), followed by 6 weeks at 1 dose level bid (days 43 to 84) during the treatment period. participants could then opt to participate in the extension period. the study consisted of 2 optional extension periods, the first through week 48 and the second through week 96. for participants who did not continue into the optional treatment extension, the study included a 2-week follow-up period.

Eligibility criteria:
inclusion criteria: * males between 18 and 55 years of age (inclusive) * hemizygous for fabry disease * had a confirmed diagnosis of fabry disease with a documented missense gene mutation (individual or familial) * had enhanceable enzyme activity * in the judgment of the investigator, were either able to safely suspend ert throughout the study, or be ert naive * agreed to be sexually abstinent or use a condom with spermicide when engaging in sexual activity during the course of the study and for a period of 30 days following completion of the study * were willing and able to sign an informed consent form exclusion criteria: * history of significant disease other than fabry disease (for example, end-stage renal disease; class iii or iv heart disease \[per the new york heart association classification\]; current diagnosis of cancer, except for basal cell carcinoma of the skin; diabetes \[unless hemoglobin a1c ≤8\]; or neurological disease that would have impaired the participant's ability to participate in the study) * history of organ transplant * serum creatinine \>2 mg per deciliter on day -2 * screening 12-lead electrocardiogram demonstrating corrected qt interval \>450 milliseconds prior to dosing * taking a medication prohibited by the protocol: fabrazyme® (agalsidase beta), replagal™ (agalsidase alfa), glyset® (miglitol), zavesca® (miglustat), or any experimental therapy for any indication * participated in a previous clinical trial in the last 30 days * any other condition, which, in the opinion of the investigator, would jeopardize the safety of the participant or impact the validity of the study results

Keywords: amicus therapeutics at1001 galafold migalastat substrate